Ascaris lumbricoides, intestinal round worms, infect 23% of the world's population. Infestation is prominent in third world countries and it compromises the nutrition available to its hosts because Ascaris are parasites and may consume 200-300 calories per day. The extent to which they may be disease sectors transmitting viruses is still unknown. Current control is with chemical anthelmintics directed only at adult worms capable of propagating themselves at the rate of hundreds of thousands per day. So long as the infected hosts live in an environment in which their food sources and waste disposal are not separated, reinfestation is imminent and chemical de-worming is of limited use. We believe the protease inhibitors in the parasite are critical to their survival, perhaps their species specificity, and the most logical site to direct an attack at biologically controlling their migration through their hosts. This approach will interrupt the life cycle of the parasite by preventing their development to adults. The approach is to examine each of the inhibitors from hog Ascaris as pure chemicals: isolate them, find their reactive sites, determine their complete amino acid sequence and study their binding to host proteases. During this project period it will be possible to examine these same compounds from Ascaris captured from humans to see if they contribute to species specificity. Studies to determine what role these inhibitors play in adults and developing larvae are ongoing. It was shown during this project period that host proteins from the environment of the worm, trypsin and chymotrypsin, enter adult worms and are also present inside of infective (2nd stage) larvae. Under natural conditions these larvae migrate through the host and progress to third stage larvae in the lungs. In the natural host they are coughed up, swallowed, and some develop to adults. In the wrong host, the larvae do not complete their life cycle. Sterling cultures of lung stage larvae raised in their natural host will be established and the role of stomach and pancreatic secretions containing natural environmental proteins will be used to try to complete their life cycle and determine which of the inhibitors might be the best candidate(s) for an attack.